The Effect Of ATRA On The Endothelium Dependent Diastolic Function Of AS Rabbits And Its Mechanism

Objective To investigate the effects of ATRA on the endothelium dependent diastolic function of atherosclerosis rabbits and its mechanism.Methods New Zealand white rabbits were randomly divided into 3 groups: the normal group were fed on standard diet;the model group were fed on high-fat diet(standard diet supplemented with 1%cholesterol+ 5%lard);ATRA group were fedon high-fat diet and(5 mg/kg/day)administered orally.After 8 weeks,experimental rabbits were sacrificed to get blood,blood lipids were tested with a kit.The formation of lipid plaque was observed by oil red staining and the change of endothelial structure was watched by HE staining.The endothelium dependent diastolic function of atherosclerosis rabbits was evaluated by high-resolution ultrasound and isolated arterial rings.Immunohistochemical staining was used to detect the expression of MLCK in rabbit thoracic artery.The expression of MLCK and MAPK signal cascades related proteins in the thoracic artery was tested by western blot.Results A high-fat diet for 8 weeks,the atherosclerosis model was successfully constructed,and ATRA could inhibit the development of atherosclerosis.Compared with the normal group,the triglyceride(TG),total cholesterol(TCH),low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c)in the serum increased significantly(P<0.05);Oil red staining showed the lipid plaque was obvious.HE staining showed that the intima was thickened,the foam cells increased,and the vascular smooth muscle cell polarity was disordered and migrating to the intima.Endothelium-dependent dilatation was significantly reduced(P<0.05)in isolated arterial rings and high-resolution ultrasound.The expression levels of MLCK and MAPK signaling pathway related proteins(P38,JNK,ERK)were significantly increased(P<0.05).Compared with the model group,in ATRA group,there was no difference in the concentration of TG,HDL-c,LDL-c.The concentration of TCH decreased significantly(P<0.05)Oil red staining revealed that the lipid plaque was visible.HE staining indicated that compared with the model group,the intima of ATRA group was slightly thickened,foam cells were reduced,and arrangement of the smooth muscle cells was more neatly.The endothelium dependent diastolic function improved significantly(P<0.05).The expression levels of MLCK and MAPK signal pathway related proteins(P38,JNK,ERK)was significantly decreased(P<0.05).Conclusions High fat diets can lead to atherosclerosis and arterial endothelial injury.The endothelial dysfunction causes endothelium dependent diastolic function to drop off,and ATRA decreases the concentration of total cholesterol in serum.ATRA improves endothelial dependent vasodilation function in atherosclerosis rabbits,and its mechanism may be related to the inhibition of MLCK expression by MAPK signaling pathway.